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Geron Sees Anticancer Activity in Lab Study

ABC News Money, January 5, 2010

The stem cell company Geron reported successful animal data in its anticancer drug candidate imetelstat. Geron was founded by Michael West with the vision of extending human life through understanding of the enzyme telomerase and developing stem cell therapy. In the area of stem cell therapy, Geron is the first company ever to have held an open IND on an embryonic stem cell based approach. The work Geron funding on telomerase received a Nobel Prize.

Telomerase is an enzyme that allows cells to escape death. With each cell multiplication the ends of the chromosome's, called telomeres, become shorter. After approximately 50 doublings the telomeres reach a critical limit and as a result the cells die or become senescent. Cells that express the enzyme telomerase are immune from this process. Essentially what the telomerase enzyme does is it fixes the ends of the chromosomes after each cell division so that the cell can essentially live forever. Normal cells that express telomerase include memory T and B cells, as well as some types of stem cells. Embryonic stem cells express a lot of telomerase and this is one of the reasons why they can be kept alive in tissue culture for years and in the case of mouse embryonic stem cells, decades.

Geron owned the intellectual property for the enzyme telomerase and methods of modulating it. Given that telomerase is expressed at very high concentrations in cancer cells, the company has been using its knowledge of telomerase to make small molecule drugs that block telomerase activity. One such drug is imetelstat, also known as GRN163L, which is in clinical trials for lung and breast cancer, was recently demonstrated to inhibit glioblastoma and stem cells of glioblastoma. IIn the study, tumors were implanted into mice and imetelstat inhibited 60 percent to 70 percent of the tumors in up to five days.

Researchers at the UT Southwestern Medical Centre, who conducted the work stated that the study on glioblastoma will appear in the January issue of Clinical Cancer Research. A study demonstrating analogous results in prostate cancer is available online in the International Journal of Cancer.

Glioma is the most common and most aggressive type of primary brain tumor. It represents 52% of all brain tumors and is highly resistant to radiation and chemotherapy. As the name implies, glioma usually originates from the glial cells of the brain, which normally act as the "support cells" for neurons. Other approaches towards glioma include: a) differentiation agents which cause the glioma stem cell to make "daughter cells" that then are capable of being killed by chemo/radiation therapy; b) immune therapy in which T cells are programmed (either in vitro or in vivo) to attack proteins found on glioma cells but not other cells; and c) nanotechnology-based strategies in which the extremely small particles are injected into the bloodstream that have some selectivity for glioma cells, and which deliver toxic payloads.

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